Bacterial meningitis is an inflammatory disease of the central nervous system caused by the growth of bacteria in and adjacent to the leptomeninges. Meningitis is an acute infectious disease which affects children and young adults and is caused by the Neisseria meningitidis, amongst other agents including other bacterial and viral pathogens.
Meningococci are subdivided into serological groups depending on the presence of either capsular or cell wall antigens. Currently recognized sero-groups include A, B, C, D, W-135, X, Y, Z, and 29E as segregated by seroagglutination. The polysaccharides responsible for the serogroup specificity of the group A, B, C, X, W-135 and Y have been purified.
The carrier rate for meningococci is much higher than the incidence of the disease. Some persons are temporary carriers, while others are chronic carriers, discharging meningococci either more or less continuously or in a sporadic fashion. The meningococcal carrier state is an immunizing process, and within two weeks of colonization, production of antibodies to meningococci can be identified. It appears that bactericidal antibodies are directed against both the capsular polysaccharide and other cell wall antigens.
Studies have shown that meningococcal outer membranes have three to five major proteins, with the predominant 41,000 Mr or 38,000 Mr proteins carrying the serotype specific determinants. There is a considerable degree of interstrain heterogeneity in the profiles of the outer membrane proteins on sodium dodecyl sulfate-polyacrylamide electrophoretic gels (SDS-PAGE). As defined by peptide mapping studies, the proteins comprise five classes, designated 1 through 5, based upon common peptide structures. Bactericidal monoclonal antibodies have been produced against the 46,000 Mr Class 1 proteins which are shared to some extent among strains of different serotypes. (Frasch, C. E. et al., (1985) pg. 633, “New Developments in Meningococcal Vaccines”, in G. K. Schoolnik et al. (ed.) The Pathogenic Nisseriae, American Society for Microbiology, Washington, D.C.).
The capsular polysaccharide of groups A, C, W-135 and Y meningococci have been used to develop vaccines against the organism. Although these vaccines have been effective in the short term, they do not induce immunological memory and subjects must be revaccinated within approximately 3 years to maintain their resistance. The group B polysaccharide is poorly immunogenic and successful vaccines have not been produced. A possible explanation for the low activity may be due to tolerance to the group B polysaccharide induced by crossreactive antigens found in human tissues such as the brain. Furthermore, studies show that most of the bactericidal antibodies in the convelescent sera of patients who have had group B meningococcal disease are directed against outer membrane proteins.
Vaccines for protecting against group B meningococcal disease have been developed in which non-covalent complexes of outer membrane proteins (OMP) and group B polysaccharide were administered. Beuvery, et al. (1983) Infect. Immun. 40:369–380. However, the B polysaccharide is known to induce a transient IgM antibody response, which does not confer immunoprotection. Furthermore, there is great antigenic diversity and variability in the meningoococci outer membrane proteins from strain to strain. Additionally, lipopolysaccharides are present in the OMP and exhibit antigenic variability as well.
There is a need for safe and effective vaccines against meningococcal disease which provide immunity from infection, particularly in infants and the elderly.